Method and device for assessing perfusion failure in a patient by measurement of blood flow

ABSTRACT

Methods and devices are provided for assessing impairment of blood circulation in a patient, such as that in perfusion failure, by measurement of blood flow in the gastrointestinal tract or upper respiratory/digestive tract of the patient. The method comprises introducing a blood-flow sensor into the gastrointestinal tract or the upper respiratory/digestive tract of a patient, placing the sensor adjacent a mucosal surface therein, and measuring blood flow in adjacent tissue to determine blood flow in that tissue. The method may also involve measurement of PCO 2  and/or pH in combination with the blood flow determination. The invention affords rapid measurement and detection of perfusion failure.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation-in-part of U.S. Ser. No. 09/160,224,filed Sep. 24, 1998, which is a continuation-in-part of U.S. Ser. No.09/099,293, filed Jun. 18, 1998, which is a continuation-in-part of U.S.Ser. No. 08/939,591, filed Sep. 29, 1997, which is acontinuation-in-part of U.S. Ser. No. 08/710,208, filed Sep. 13, 1996,abandoned, which is a continuation-in-part of U.S. Ser. No. 08/498,932,filed Jul. 6, 1995, which issued Dec. 3, 1996 as U.S. Pat. No.5,579,763.

TECHNICAL FIELD

The present invention relates generally to methods and devices forassessing perfusion failure in a patient. More particularly, theinvention relates to assessment of perfusion failure in a patient bymeasuring blood flow in a mucosal tissue in the body of a patient.

BACKGROUND

Very low blood flow, or low “systemic perfusion,” is typically due tolow aortic pressure and can be caused by a number of factors, includinghemorrhage, sepsis and cardiac arrest. The body responds to such stressby reducing blood flow to the gastrointestinal tract to spare blood forother, more critical organs. Thus, when there is a reduced flow of bloodfrom the heart, the body directs a higher portion of blood to criticalorgans, such as the brain, which will not survive long without acontinuous supply of blood, while restricting the flow to less criticalorgans, whose survival is not as threatened by a temporary largereduction in blood flow. For example, blood flow to the splanchnicvasculature which supplies the stomach and intestines, and also theesophagus and oral/nasal cavity, is drastically reduced when there is areduced blood flow from the heart. For this reason, decreased blood flowto the splanchnic blood vessels is thus an indication of perfusionfailure in a patient. Physicians commonly take advantage of thisphenomenon by taking CO₂ and pH measurements in the stomach andintestine to assess perfusion failure.

Assessment of CO₂ concentration in the less critical organs, i.e., thoseorgans to which blood flow is reduced during perfusion failure, has beenuseful in perfusion assessment. Carbon dioxide production, which isassociated with metabolism, continues in tissues even during conditionsof low blood flow. The concentration of CO₂ builds-up in tissuesexperiencing low blood flow because CO₂ is not rapidly carried away.This CO₂ build-up (an increase in partial pressure of CO₂ (PCO₂)) in theless critical organs in turn results in a decrease in pH in nearbytissue. Therefore, perfusion failure is commonly assessed by measuringpH or PCO₂ at these sites, especially in the stomach and intestines. Forexamples of catheters used to assess pH or PCO₂ in the stomach orintestines, see, e.g., U.S. Pat. Nos. 3,905,889; 4,016,863; 4,632,119;4,643,192; 4,981,470; 5,105,812; 5,117,827; 5,174,290; 5,341,803;5,411,022; 5,423,320; 5,456,251; and 5,788,631.

The inventors have found that increases in PCO₂ may be measuredthroughout the body, including in accessible organs and tissues fed bysplanchnic vessels, and used to assess perfusion failure. For example,the inventors have found that a useful measurement of perfusion failurecan be obtained by measuring CO₂ in the upper respiratory/digestivetract. In U.S. Pat. No. 5,579,763, a method is described that can beused to accurately assess perfusion failure by measuring PCO₂ in thepatient's esophagus, rather than in the less accessible stomach and/orintestine as previously practiced in the art. Tests showed thatmeasurements of PCO₂ in the esophagus are closely correlated with aorticpressure, and, furthermore, that measurements made in the esophagus areeven more closely correlated to aortic pressure than measurements of CO₂in the stomach. More recently, in co-pending, commonly assigned U.S.Ser. No. 09/160,224, the inventors further showed that PCO₂ measurementsin a patient's mucosal tissues (e.g., mouth, nasal mucosa, and throat)are also closely correlated to aortic pressure. As disclosed in U.S.Ser. No. 09/160,224, the CO₂ sensor may be placed at a site within theoral-nasal cavity (e.g, under the tongue at a site in contact with thetongue or the floor of the mouth) where it effectively measures CO₂ inthe tissue. Since carbon dioxide can readily pass through mucosalsurfaces, CO₂ generated by metabolic activity occurring in tissue belowthe mucosal surface that is not carried away by blood flow readilymigrates through the mucosal surface, where its build-up provides a goodmeasure of perfusion failure. Placement of a CO₂ sensor adjacent amucosal surface of the upper respiratory/digestive tract thus provides avery good quantification of perfusion failure at all times, includingthe most critical minutes after the onset of perfusion failure whentreatment is likely to be most effective. Thus, mucosal measurements oftissue perfusion can be used to assess perfusion failure in patients.

However, PCO₂ and pH are indirect measures of blood flow in tissue,being based upon the build-up of metabolites that result from poorperfusion. In addition, measurements of pH may be complicated by thepresence of saliva, food, or stomach acids. CO₂ measurements may beaffected by ambient CO₂, and, since they depend on equilibration withtissue CO₂ levels, are slow. Thus, there is a need for a more directmethod for measuring blood flow in a tissue, to more accurately assessperfusion failure and to monitor the effectiveness of methods taken toincrease perfusion, e.g., blood infusion or the like.

SUMMARY OF THE INVENTION

Methods and devices are provided for assessing impairment of circulatoryfunction in a patient, such as that in perfusion failure, by measurementof blood flow in the GI tract and/or upper respiratory/digestive tractof a patient. The perfusion of a tissue is a function of both thevelocity of blood cells flowing through tissue, and of the number ofblood cells, so that the blood flow through tissue is a more directmeasurement of tissue perfusion than pH or CO₂ measurements. Previously,the belief in the art was that decreased blood flow was a localizedphenomenon during perfusion failure. It has now been discovered thatdecreased blood flow, decreased pH and increases in tissue CO₂ occurthroughout the body during perfusion failure, and in particular occurnot only in the stomach, jejunum, colon and rectum, but also in theesophagus, throat, mouth and nose. Thus, new and useful methods anddevices are now provided, for assessing perfusion failure and perfusionlevels in a patient by measuring blood flow in tissues of the GI tractand/or of the upper respiratory/digestive tract of a patient.

In one embodiment, then, a method is provided for assessing impairmentof circulatory function, such as that in perfusion failure, in apatient. The method comprises introducing a blood-flow sensor into theGI tract or into the upper respiratory/digestive tract of a patient,measuring blood flow in the tissue adjacent the sensor, and providingthat measurement for assessment of perfusion failure. Specifically, ablood-flow sensor is placed adjacent a mucosal surface within apatient's body, preferably without passing the sensor down through orbeyond the patient's epiglottis, most preferably within the oral or anasal cavity of the patient. The blood-flow sensor is preferablyintroduced sublingually, and preferably to one side of the frenulum. Theinvasiveness of such a technique is minimal, being substantially no morethan in the use of an oral thermometer. Preferably, the sensor is alaser-Doppler sensor. The output of the sensor can be detected by adevice which electronically converts the sensor output to provide theblood flow in a form that is easily understood by persons viewing thedisplay. The device can optionally further sense the rate of change ofblood flow with time to indicate the patient's condition.

Accordingly, in another embodiment the invention features a device forassessing perfusion failure in a patient, where the device is composedof a laser-Doppler blood-flow sensor means for measuring blood flow in atissue, the sensor means being adapted for lying adjacent a mucosalsurface in a patient's body, e.g. in the upper respiratory/digestivetract of a patient, and measuring blood flow in vessels in the mucosaltissue; and an indicating means connected to the sensor means, whereinthe indicating means indicates a degree of perfusion failure of thepatient associated with the detected blood flow. The device may alsoinclude a positioning means for positioning the sensor means adjacentthe mucosal surface. In a preferred embodiment, the “positioning means”is a holder designed to fit within the mouth of the patient and hold thesensor in place adjacent the mucosal surface. For example, the holdermay be designed to position the sensor adjacent the tongue of a patient,or to position the sensor between the inside of a lip and gum of thepatient. Alternatively, the positioning means may be a holder designedto fit within a nares of the patient and hold the sensor in placeadjacent the mucosal surface.

In a further embodiment the invention features a device for use with ablood-flow sensor assembly for assessing perfusion failure of a patient.The device is composed of a sensor holder with a sublingual holder innerportion shaped to fit in the mouth of a patient under the patient'stongue, said holder forming at least one holder passage optionallyextending from said holder outer portion to said sublingual holderportion.

In a further embodiment the invention comprises measuring blood flowwith a blood-flow sensor and additionally making an indirect measurementof blood flow by making, e.g., a CO₂ measurement or a pH measurement, orby making all three such kinds of measurements.

One advantage of the invention is that perfusion can be rapidly assessedin a patient, with measurements being made in just a few seconds.

Another advantage of the invention is that perfusion can be assessed ina patient in a minimally invasive manner, and with minimal discomfort orrisk of harm to the patient.

Another advantage of the invention is that perfusion can be assessed ina patient without interference in the measurement by ambient levels ofCO₂ and without substantial drift of the measurement when used in acontinuous monitoring application.

Another advantage of the invention is that perfusion can be assessed ina patient without interference with the measurement by the pH of fluidsor food near the sensor.

Another advantage of the invention is that perfusion can be readilyassessed in a patient suffering from perfusion failure associated withany of a variety of causes, including, but not limited to physicaltrauma, infection, hypothermia, cardiogenic shock (e.g., acutemyocardial infarction, aneurysm, or arrhythmia), obstructive shock(e.g., pulmonary embolism), hypovolemic shock (e.g, due to hemorrhage orfluid depletion), and distributive shock (e.g., due to sepsis, exposureto toxins, or anaphylaxis). The sensitivity of the methods and devicesof the invention further allow for assessment of perfusion across a widerange of perfusion failure severity, thereby providing a means toaccurately monitor the patient's condition.

Still another advantage of the invention is that the devices and methodscan be readily adapted for use in alert, semi-conscious, or unconsciouspatients, and can be further adapted for accurate assessment ofperfusion in a patient for a period lasting for only seconds to minutesto hours or days.

The novel features of the invention are set forth with particularity inthe appended claims. The invention will be best understood from thefollowing description when read in conjunction with the accompanyingdrawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a graph showing variation in blood flow in various tissueswith time, during an experiment on rats where blood was withdrawn tosimulate hemorrhage and so induce perfusion failure, and duringreinfusion of blood to allow recovery.

FIG. 2 is a partial sectional view showing a sensor of the presentinvention in place in one of many acceptable positions within the GItract of a patient.

FIG. 3 is an isometric view showing a sensor of the present invention asit is introduced into the mouth of a patient, for sublingual placement.

FIG. 4 is a sectional view of a sensor assembly and holder constructedin accordance with an embodiment of the invention, shown lying in apatient's mouth.

FIG. 5 is an isometric view of the holder of FIG. 4.

FIG. 6 is a sectional view of a sensor assembly and holder of anotherembodiment of the invention, shown holding a sensor between a lip andteeth of a patient.

FIG. 7 is a front isometric view of the holder of FIG. 6.

FIG. 8 is a sectional view of a sensor assembly and holder of anotherembodiment of the invention, shown holding a sensor in the nose of apatient.

DETAILED DESCRIPTION OF THE INVENTION

Definitions and Nomenclature

Before the present devices, apparatus and methods are disclosed anddescribed, it is to be understood that this invention is not limited tosensor designs, measurement techniques, or the like, as such may vary.It is also to be understood that the terminology used herein is for thepurpose of describing particular embodiments only and is not intended tobe limiting.

It must be noted that, as used in the specification and the appendedclaims, the singular forms “a,” “an” and “the” include plural referentsunless the context clearly dictates otherwise.

The term “perfusion failure” as used herein is meant a reduction inblood flow associated with maldistribution of blood through thecirculatory system and a reduction in blood low to a less criticaltissue(s) and/or organ(s) relative to blood flow in vital (critical)tissues and organs (e.g., the brain and heart). In general, “perfusionfailure” is meant to encompass reduction in blood flow associated with adecrease in blood flow significantly or substantially below thatassociated with normal perfusion.

The term “measurement” as used herein refers to a single measurement ora series of measurements made over time, and which may be takencontinuously or intermittently (e.g., at selected time intervals).

The term “mucosal surface” as used herein refers to a surface of amucous membrane containing or associated with mucus secreting glands,and which lines body passages, tubular structures, and organs andencompasses, for example, the nasal passages, the oral passage, thenasopharynx, the throat, the esophagus, the stomach, the jejunum, thecolon, and the rectum.

The terms “gastrointestinal tract” and “GI tract” as used hereinencompass the entire tract from esophagus to rectum, including, e.g.,the esophagus, the stomach, the jejunum, the colon, and the rectum.

The term “upper respiratory/digestive tract” as used herein means theregion of the upper respiratory tract and digestive tract above thestomach. In general, the “upper respiratory/digestive tract” encompassesthe nasal passages (including the nares and nasal cavities), the oralpassage (including the mouth and spaces within the mouth such as thefloor (e.g., sublingual area) and roof of the mouth (e.g., hard palate),the soft palate, the regions between the lips and gums, and the cheeksand gums), the nasopharynx, the throat and esophagus. The term“oral-nasal cavity” as used herein means the region of the

The term “oral-nasal cavity” as used herein means the region of theupper respiratory/digestive tract encompassing the nasal passages(including the nares and nasal cavities), the oral passage (includingthe mouth and spaces within the mouth such as the floor (e.g.,sublingual area) and roof of the mouth (e.g., hard palate), the softpalate, the regions between the lips and gums, and the cheeks and gums),and the nasopharynx and the throat extending to the top surface of andin the region of the epiglottis.

The term “sublingual” as used herein refers to a region below or beneaththe tongue.

The term “adjacent” as used herein (e.g., “adjacent the mucosalsurface”) means near or against, e.g., at a distance from the mucosalsurface that allows acceptably accurate measurement of blood flow byblood-flow sensor.

The term “patient” as used herein means a mammalian subject, preferablya human subject, that has, is suspected of having, or is or may besusceptible to a condition associated with low blood flow, and thusperfusion failure.

The present invention is based on the inventors' discovery that bloodflow decreases throughout the body during perfusion failure, rather thanas only a localized phenomenon as previously believed in the art.Evidence for this is seen, e.g., in that tissue CO₂ increases inesophagus and sublingual tissue during perfusion failure, as disclosedby the inventors in U.S. Ser. No. 09/160,224. Further evidence of thisis shown in FIG. 1 where blood flow in various tissues of experimentalanimals was measured by the deposition of small beads measured atautopsy. The methods and devices of the invention measure blood flow intissue at a convenient site within the GI tract or within the upperrespiratory/digestive tract, and are thus performed in a minimallyinvasive manner. In general, these measurements are made by placing ablood-flow sensor such as a laser-Doppler sensor or an ultrasoundDoppler adjacent a mucosal surface at a selected site within the upperrespiratory/digestive tract and using the sensor to measure blood flowat the selected site. Such measurements may also be made using imagingtechniques such as MRI, optical imaging, angiography techniques andother methods as would be known to those skilled in the art.

As blood flows through tissue, the blood cells and the fluid bloodplasma move at similar rates. Light, as may be provided by alaser-Doppler blood-flow device, and ultrasound, as may be provided byan ultrasound-Doppler blood-flow device, can pass through tissue toilluminate or impinge upon blood cells moving through tissue ofinterest. When light or ultrasound reflects off moving blood cells itsfrequency is shifted in a velocity-dependent manner, a phenomenon knownas the “Doppler shift.” This phenomenon can be used to measure thevelocity of blood cells flowing through the tissue so illuminated or sosubject to ultrasound. In addition, a laser-Doppler device orultrasound-Doppler device may be used to measure the ratio of movingblood cells to the non-moving cells located in the measurement volume ofthe sensor. The measurement volume of tissue in which this measurementis made may be calculated using scattering theory and the geometry ofthe illuminating and collecting sites, or may be measured using standardcalibration techniques; either of which is routinely done withlaser-Doppler devices. The total blood flow may be calculated from thesethree parameters: 1) the number of cells within the measurement volume,2) the velocity of the moving cells, and 3) the measurement volume.

Methods and techniques for using laser-Doppler techniques and devices tomeasure blood flow are known in the art, and may be found in suchreferences as, e.g., U.S. Pat. No. 3,511,227 to Johnson, U.S. Pat. No.4,596,254 to Adrian et al., and U.S. Pat. No. 4,590 ,948 to Nilsson.

Methods and techniques for using ultrasound-Doppler techniques anddevices to measure blood flow are known in the art, and may be found insuch references as U.S. Pat. No. 4,324,258 to Huebscher et al. and U.S.Pat. No. 4,759,374 to Kierney et al.

Thus, laser-Doppler, ultrasound-Doppler, and other blood-flowmeasurement devices can be used to provide direct measures of blood flowin tissues. The present invention provides novel methods using suchmeasurements to detect and quantify blood flow in tissues susceptible tolow blood flow effective to detect perfusion failure in a patient.

In order to assess perfusion failure in a patient, one first determinesthe expected range of blood-flow measurements for subjects of similarage and health status as the patient. Normal levels of blood flow mayvary with the age of the subject. Health status may also be an importantvariable, since, for example, blood flow in a diabetic subject maydiffer from that of a subject not suffering from diabetes. Next, theblood flow in a mucosal tissue of the patient is determined. Theblood-flow value is compared with the expected value for a normalsubject determined in the first step; patient blood-flow values that aresignificantly lower than the normal values indicate perfusion failure.In addition, the rate-of-change of the patient's blood flow is measuredover time with the blood-flow sensor. Rising values of blood flowindicate recovery, while declining values of blood flow indicate aworsening of the patient's condition.

The correlation of perfusion failure with decreased blood flow inseveral bodily tissues, including sublingual blood flow in particular,as well as the correlation of perfusion recovery and a correspondingincrease in sublingual blood flow as blood volume recovers, was testedin an animal model that simulates a sudden loss or shedding of blood,such as might be caused by a gunshot wound or other severe wound.Perfusion recovery was simulated by subsequently reperfusing the animalswith a blood infusion. Blood flow in the several tissues was assessed bycounting (at autopsy) the numbers of colored microspheres deposited invarious tissues under the indicated conditions, as described in Hale etal. (Circulation 78:428-434, 1988). The results are shown in FIG. 1.Blood flow in a tissue as a percentage of baseline (control) blood flowis plotted as a function of time during hemorrhage (induced blood-loss)and reinfusion of blood in an experimental animal. At the beginning ofthe test (BL), just prior to the time-point labeled “0,” considerableblood was drawn from an animal that was previously in good health, theblood being drawn within a period of a few minutes. Aortic pressuredrops rapidly during the first few minutes of such a test. In asubsequent period of about two hours, the aortic pressure remained about40-50% below normal. The graph shows that tongue and sublingual bloodflow decreased to about 35% during the first hour, showing a moredramatic response than other tissues. These data show that an decreasein sublingual blood flow is directly correlated with the effects ofblood loss, i.e. perfusion failure.

The relationship of sublingual blood flow and recovery of blood volume(i.e., during perfusion recovery) was tested by infusing the animal witha blood infusion at 120 minutes. Aortic pressure rapidly increasesduring this period; similarly, sublingual blood flow rapidly recovered.

In addition to blood flow, as described above, PCO₂ or pH may also bemeasured in the animal or patient, at the same time or shortly before orshortly after such blood-flow measurements are made, to provide furtherinformation useful for assessing perfusion failure in an animal or apatient. PCO₂ and pH may be measured using any suitable technique, aswill be appreciated by those skilled in the art.

For example, PCO₂ may be measured using a CO₂ sensor such as apH-sensing PCO₂ sensor. Such PCO₂ sensors may have, for example, amembrane that is permeable to CO₂, and that separates a sodiumbicarbonate or carbonic acid (HCO₃) solution from the environment. A pHsensor in the device measures the pH of the sodium bicarbonate solution.Two exemplary CO₂ sensors of this type are manufactured byMicroelectrode, Inc. and Nihon Kohden (ISFET PCO₂ sensor).

Alternatively, the CO₂ sensor is an optical PCO₂ sensor. Structures,properties, functions, and operational details of fiber optic chemicalsensors can be found in U.S. Pat. Nos. 4,577,109; 4,785,814; and4,842,783, as well as in Seitz, “Chemical Sensors Based on FiberOptics,” Anal. Chem. 56 (1):16A-34A (1984). Fiber optic sensors formonitoring CO₂ that may be suitable for use in the present inventioninclude, but are not limited to, those described in U.S. Pat. Nos.4,800,886; 4,892,383; 4,919,891, 5,006,314, 5,098,659; 5,280,548; and5,330,718. Other exemplary fiber optic CO₂ sensors are described inPeterson et al. “Fiber Optic Sensors for Biomedical Applications,”Science 224(4645):123-127 (1984) and Vurek et al. “A Fiber Optic PCO₂Sensor,” Annals Biomed. Engineer. 11:499-510 (1983).

A suitable optical CO₂ sensor is described in U.S. Pat. No. 5,714,121('121) to Alderete et al., which pertains to an optical CO₂ sensor andmethod of manufacture thereof; a preferred sensor system and method ofusing the aforementioned optical CO₂ sensor is described in U.S. Pat.No. 5,672,515 ('515) to Furlong. In general, the sensor of the '121patent is composed of a single optical fiber having a distal tip and aproximal region for communication with a means for receiving a signalfrom the distal tip. Light of a predetermined wavelength is directedthrough the optical fiber towards the distal tip, and emittedfluorescent light returns along the fiber to be detected and convertedto a CO₂ concentration value. A capsule, composed of a CO₂-permeablesilicone material, is arranged over the distal tip at a predeterminedposition. The capsule contains an indicator solution having a suitablepH-sensitive indicator component, generally a fluorescent dye, andsubstantially no air. Examples of fluorescent dyes include withoutlimitation fluorescein, carboxyfluorescein, seminaphthorhodafluor,seminaphthofluorescein, naphthofluorescein, 8-hydroxypyrene1,3,6-trisulfonic acid, trisodium salt (“HPTS”) and dichlorofluorescein,with HPTS particularly preferred. A sealing means provides aliquid-tight seal and affixes the capsule onto the distal tip.

Optical CO₂ sensors are generally used by contacting the distal end ofthe sensor with a mucosal surface as described herein. Light of apredetermined wavelength is directed from an external source, throughthe optical fiber, impinging distally on the encapsulated indicatorcomposition. The intensity of the emitted fluorescent light returningalong the fiber is directly related to the concentration of CO₂ in thesample, as a result of the pH-sensitive indicator material present atthe fiber tip (i.e., the pH of the indicator solution is directlyrelated to CO₂ concentration, as a result of carbonic acid formation).The emitted light is carried by the optical fiber to a device where itis detected and converted electronically to a CO₂ concentration value.The sensor may additionally have a reference dye present in theindicator composition. The intensity of the light emitted from thereference dye may be used to compensate, via ratioing, the signalobtained from the indicator. A more preferred system for determiningPCO₂ is described in the '515 patent, directed to a simultaneous dualexcitation/single emission fluorescent sensing method, wherein light oftwo different wavelengths is used to excite a single fluorescentindicator species, with one of the two wavelengths at the isosbesticpoint. The two fluorescence emission signals that result are ratioed toprovide the desired measurement.

Suitable pH sensors include optical pH sensors as described in U.S. Pat.Nos. 5,536,783 and 5,607,644 to Olstein et al. Such optical sensorsinclude a chemical pH sensor means, capable of responding to changes inpH in nearby tissues and fluids, that is incorporated into a fiber opticwaveguide assembly so as to interact with the environment into which thepH sensor means is placed. The sensor may be placed in a patient's body,and more particularly, may be placed adjacent a mucosal surface in apatient's body. Typically, the responses of the chemical sensor causechanges in the optical properties of the chemical sensor/opticalwaveguide assembly, so that pH changes near the tip of the assembly maybe monitored and assessed by the user at another portion of theapparatus, e.g., at a portion of the apparatus remaining external to thepatient's body. For example, as described in the aforementioned U.S.patents, the pH sensor means may comprise a fluorescent poly(urethrane)copolymer that fluoresces in response to irradiation, wherein thefluorescence is dependent on the pH of the environment being monitored.

The results of experiments in the animal model, as shown in FIG. 1, canbe extrapolated to represent a human subject suffering perfusionfailure, such as that associated with a gunshot wound or a severe cutfrom machinery or a knife. Thus, a patient will suffer a rapid decreasein aortic pressure during blood loss, until the outflow of blood isstopped by application of pressure or other means to stop bleeding. Thepresent invention takes advantage of the relationship between blood flow(in the GI tract or the upper respiratory/digestive tract, including insuch tissues as sublingual, tongue, stomach and so forth) and perfusionfailure or perfusion level, to provide methods and devices to assist aphysician or other health care provider in the diagnosis and treatmentof a patient having or susceptible to a condition associated withperfusion failure.

For example, although assistance from a paramedic or other person may beavailable shortly after the initial primary insult, it may take thirtyminutes or more for the patient to reach a hospital. This lapse in timemay make it difficult to accurately assess the condition of the patientand the presence and/or severity of perfusion failure. Measuring and/ormonitoring sublingual blood flow according to the present inventionallows the physician or other healthcare provider to readily detect thelevel of blood flow relative to normal, as well as the rate of change ofblood flow. A rapid decrease in blood flow suggests that the patient hassuffered a loss of blood within the last hour or so, while low bloodflow indicates the patient presently suffers from a low level of aorticpressure and perfusion failure. In this manner the invention can be usedto assess the patient's condition, allowing for appropriate and rapidselection of an appropriate therapy.

The present invention can also be used to monitor the efficacy ofreperfusion or other therapeutic regimen to treat perfusion failure inthe patient. For example, if the physician, paramedic, or otheremergency provider determines that a transfusion of blood or bloodcomponents is indicated, and the transfusion is successful in rapidlyincreasing aortic pressure (such as that illustrated in FIG. 1 from 120minutes onward), then this success will be reflected by a rapid recoveryin blood flow (as illustrated in FIG. 1 from 120 minutes onward). FIG. 1shows that sublingual blood flow measurements provide a good indicationof the level of perfusion failure.

In the present invention, the inventors disclose that a usefulmeasurement of perfusion failure can be obtained by measuring blood flowanywhere in the GI tract or the upper respiratory/digestive tract.Although FIG. 2 illustrates the upper portion of the GI tract, it is tobe understood that the invention may be practiced by placement of ablood-flow sensor in any portion of the GI tract or upperrespiratory/digestive tract. Accordingly, by way of illustration, FIG. 2shows the upper respiratory/digestive system or tract A of a person, andparticularly including the nasal passage B, the oral passage C, and theupper portion D of the throat that extends to the top of the epiglottisE. The upper respiratory/digestive tract includes the esophagus F, andthe gastrointestinal tract includes the esophagus F, the esophagealsphincter G, the stomach H, and the intestines J. Insertion of acatheter 10 with a blood-flow sensor 12, through the nasal or oralpassage B, C, past the epiglottis E, and into the esophagus F so thatthe end 14 of the catheter with the sensor 12 thereat lies within theesophagus.

Preferably, the sensor may be positioned in the upperrespiratory/digestive tract A, preferably with the sensor lying above,at the surface of, or at the epiglottis E so it does not have to pass byit. More preferably, the sensor is placed at a site within theoral-nasal cavity, e.g., within a nasal cavity, the mouth (e.g., underthe tongue at a site in contact with the tongue or the floor of themouth, between a region of the lip and gum or the cheek and gum, theroof of the mouth, or the soft palate), or the nasopharynx. Mostpreferably, the sensor is placed at a site that will avoid the patient'sgag reflex or otherwise minimize discomfort.

The blood-flow sensor lies adjacent a mucosal surface in the upperrespiratory/digestive tract A, in order that it effectively measuresblood flow in the tissue. Placement of a blood-flow sensor adjacent amucosal surface of the upper respiratory/digestive tract A according tothe present invention provides a very good quantification of perfusionfailure at all times, including the most critical minutes after theonset of perfusion failure when treatment is likely to be mosteffective.

FIG. 3 shows one embodiment of a device or apparatus of the presentinvention, wherein a tube 20 containing a blood-flow sensor 22 at itsfront end, is inserted into the oral passage and placed under the tongueT of the patient, preferably to one side of the frenulum V. Afterinsertion, it might be desirable if the mouth M of the patient is keptclosed around the tube. However, as with other instruments commonlyinserted through the mouth, and as with a patient in a criticalcondition, the patient is usually unable to keep his mouth closed. Insuch cases the device can be adapted with a holder as described below.

As illustrated in FIG. 3, the tube 20 and sensor 22 are part of aninstrument 24 that includes a flexible cable 26 that extends to a testinstrument 30 that typically indicates the blood flow which provides anindicia of a degree of perfusion failure. While the tube 20 issubstantially rigid, the cable 26 is flexible. The cable 26 can be madehighly flexible for ease of use, instead of having only the moderateflexibility of a catheter. Usually catheters require enough flexibilityto pass through curved body passages, but yet must be resistant tocolumn-type collapse in order to withstand the force applied to thecatheter's proximal end necessary to accomplish insertion of the distalend and movement of the distal end along the body passage. Since thecable 26 in the device of FIG. 3 does not have to be pushed, it can havemore flexibility for ease of use. The largely rigid tube 20 preferablyhas a length of no more than about one foot one-third meter), since alonger length would be cumbersome. Catheters for insertion through theesophagus into the stomach, generally have a length of much more thantwo feet. FIG. 4 shows an example of a sensor 212, which lies againstthe sublingual mucosal surface.

FIG. 5 shows a preferred embodiment of the device of the invention thatis suitable for taking sublingual blood flow measurements. In thisembodiment, sensor assembly instrument 214 may be held in position by asensor holder 202 that is shaped to lie primarily in a patient's mouth.The holder 202 forms a holder passage 204 that extends between the innerand outer portions 202, 226 of the holder. When located in place, thesensor 214 projects inwardly from the holder and substantially directlycontacts the mucosal surface of the patient. The frame may have an outerend that lies outside the patient's mouth.

The holder 202 can serve to prevent discomfort to the patient. To thisend, the sublingual inner portion 226, including portions 222 and 224,of the holder preferably lies close to the walls of the mouth onopposite sides of the sensor 214, as well as above and below the sensor.The upper surface 206 of the holder is designed so the tongue T can lieon at least its inner portion, to further provide a seal and to supportthe tongue to avoid tiring the patient. The holder 202 can also serve asan aid to prevent drying of the oral-nasal cavity.

While the holder is an exemplary and preferred isolating means for usewith the present invention, other isolating means that servesubstantially the same function can be substituted or used inconjunction with the holder. For example, a sheath can surround theblood-flow sensor. The sensor and the sheath can be held in place by aholder similar to that described above, but with the advantage that theentire device may be of an overall smaller size (e.g., for placement inthe mouth).

A second purpose of the holder is to substantially fix the position ofthe sensor assembly 214 and the sensor 212 so the sensor is maintainedin a proper position and does not move. This is particularly usefulwhere the patient is incapable of holding the sensor properly in placedue to unconsciousness or some other reason. A tension coil springextending between the handle and holder, can be used to gently urge thesensor 212 inwardly, where necessary. The holder 202 is preferablyformed of an elastomeric material (Young's modulus of less than 50,000psi) such as a soft rubber or soft foam, to avoid high localizedpressure on the patient's mouth that could cause discomfort. Preferably,the sensor is positioned on either side of the frenulum of the tongue.The rear portion of the holder 226 may be shaped, as with a slot orbevel, to comfortably receive the frenulum, so the sublingual innerportion can lie close to the inner end of the sublingual area andtherefore closely around the blood-flow sensor.

Although the inventors prefers to place the sensor in a sublingual area,the sensor can be placed within any region of the GI tract or upperrespiratory/digestive tract, most preferably adjacent a mucosal surfaceof the mouth or nose. For example, in FIG. 6 the sensor 230 can beplaced at a mucosal surface W that lies between a lip X and the teeth Yof the patient. The area at the rear of the upper or lower lips X, Z isa mucosal surface. FIGS. 6 and 7 illustrate a holder 230 suitable foruse at a mucosal surface adjacent a patient's lips. In this embodiment,holder 230 is preferably of soft elastomeric material such as anelastomeric solid or a foam, or even a viscous fluid in a flexibleshell. The holder isolates the mucosal surface area contacted by thesensor and prevents movement of the sensor.

In another embodiment, the blood-flow sensor 240 lies adjacent a mucosalsurface area AA in a nares (nostril) of a patient (FIG. 8). A foam plug242 serves as a holder that holds the sensor to position it. Only a pairof electrical wires 244 extend from the sensor through the holder. Wherethe blood-flow sensor is a fiber optical sensor, the holder can beadapted accordingly so that only the optical fiber extends from theplug.

In another embodiment, the blood-flow sensor may be placed adjacent amucosal surface in the stomach of a patient.

In another embodiment, the blood-flow sensor may be placed adjacent amucosal surface in the jejunum of a patient.

In another embodiment, the blood-flow sensor may be placed adjacent amucosal surface in the colon of a patient.

In another embodiment, the blood-flow sensor may be placed adjacent amucosal surface in the rectum of a patient.

In another embodiment, a PCO₂ sensor may be used in conjunction with theblood-flow sensor. Alternatively, a pH sensor may be used in conjunctionwith the blood-flow sensor. In a further embodiment, both a pH sensorand a PCO₂ sensor may be used in conjunction with the blood-flow sensor.The advantages of such a combination in providing a more robustindication of perfusion failure will be well understood by those skilledin the art.

The blood-flow sensor used in the methods and devices of the inventionmay be any blood-flow sensor suitable for detection of blood flow in themanner described herein, such as laser-Doppler blood-flow sensors,ultrasound-Doppler blood-flow sensors, imaging sensors and so forth. Forexample, the preferred blood-flow sensor is a laser-Doppler blood-flowsensor.

An exemplary blood-flow sensor of this type is manufactured byVasomedics (2963 Yorkton Blvd., St. Paul, Minn. 55117-1064; (800)695-2737)). For example, the Laserflo BPM² may be used to providecontinuous tissue perfusion data which can be used to practice thepresent invention.

Thus, the invention provides a method and device for assessing perfusionfailure, which methods may be performed rapidly, with little equipmentset-up required, and with minimal or substantially no invasion, and thusminimal risk of harm to the patient and an improved probability ofpatient compliance. The method generally involves introducing ablood-flow sensor into the GI tract of a patient, or into the upperrespiratory/digestive tract of a patient, adjacent a mucosal surfacetherein. Furthermore, the method can be performed so as to avoid eventriggering the gag reflex of the patient by placing the blood-flowsensor in the upper respiratory/digestive tract at a position above theepiglottis, preferably sublingually. Measurements of blood flow aretaken while the sensor is held adjacent a mucosal surface in the upperrespiratory/digestive tract, such as a mucosal surface of the mouth ornose, for example the area under the tongue, an area between the upperor lower lip and the teeth, or an area in the nose. A holder may beoptionally used to prevent sensor movement The invention is useful in avariety of settings, such as in triage in emergency and disastersettings, monitoring in anesthesia, intensive care, and other acutesettings in which patients may have acute perfusion failure (shock).

It is to be understood that while the invention has been described inconjunction with the preferred specific embodiments thereof, that theforegoing description as well as the examples which follow are intendedto illustrate and not limit the scope of the invention. Other aspects,advantages and modifications within the scope of the invention will beapparent to those skilled in the art to which the invention pertains.All patents, patent applications, journal articles and other referencesmentioned herein are incorporated by reference in their entireties.

What is claimed is:
 1. A method for assessing systemic perfusion failureof a patient, the method comprising: placing a blood-flow sensoradjacent a sublingual mucosal surface within the body of a patient; andmeasuring blood flow in an adjacent tissue; wherein a measured bloodflow in the adjacent tissue that is substantially lower than a normalblood flow is indicative of systemic perfusion failure in the patient.2. A method for assessing perfusion failure of a patient, the methodcomprising: placing a blood-flow sensor adjacent a mucosal surfacewithin the body of a patient; placing a PCO₂ sensor adjacent a mucosalsurface within the body of a patient, measuring blood flow in adjacenttissue using the blood-flow sensor; and measuring PCO₂ with the PCO₂sensor, wherein a measured blood flow that is substantially lower than anormal blood flow and a PCO₂ that is substantially higher than a normalPCO₂ are indicative of perfusion failure in the patient.
 3. The methodof claim 2, wherein the mucosal surface is in the gastrointestinal tractor in the upper respiratory/digestive tract.
 4. The method of claim 2,wherein the mucosal surface is in the gastrointestinal tract.
 5. Themethod of claim 2, wherein the mucosal surface is in the upperrespiratory/digestive tract.
 6. The method of claim 2, wherein themucosal surface is in the esophagus.
 7. The method of claim 2, whereinthe mucosal surface is in the oral-nasal cavity.
 8. The method of claim2, wherein the mucosal surface is in the mouth.
 9. The method of claim2, wherein the mucosal surface is a sublingual surface.
 10. The methodof claim 2, wherein the mucosal surface is in a nasal passage.
 11. Themethod of claim 2, wherein the blood flow is measured using alaser-Doppler blood-flow sensor.
 12. The method of claim 2, wherein theblood flow is measured using an ultrasound-Doppler blood-flow sensor.13. The method of claim 2, wherein said measuring step comprises:positioning a blood-flow sensor means adjacent the mucosal tissue; andmeasuring a rate-of-change of blood flow in the mucosal tissue wherebythe rate-of-change indicates whether blood flow is decreasing, andwhereby a decreasing blood flow indicates a worsening condition in apatient.
 14. A method for assessing perfusion failure of a patient, themethod comprising: placing a blood-flow sensor adjacent a mucosalsurface within the body of a patient; placing a pH sensor adjacent amucosal surface within the body of a patient; measuring blood flow inadjacent tissue using the blood-flow sensor; and measuring pH with thepH sensor, wherein a measured blood flow that is substantially lowerthan a normal blood flow and a pH that is substantially lower than anormal pH are indicative of perfusion failure in the patient.
 15. Amethod for assessing perfusion failure of a patient, the methodcomprising: placing a blood-flow sensor adjacent a mucosal surfacewithin the body of a patient; placing a PCO₂ sensor adjacent a mucosalsurface within the body of a patient; measuring blood flow in adjacenttissue using the blood-flow sensor; placing a pH sensor adjacent amucosal surface within the body of a patient; measuring PCO₂ with thePCO₂ sensor, and measuring pH with the pH sensor, wherein a measuredblood flow that is substantially lower than a normal blood flow, a PCO₂that is substantially higher than a normal PCO₂ and a pH that issubstantially lower than a normal pH are indicative of perfusion failurein the patient.